Alzheimer's Disease
Conditions
Keywords
subjective memory complaints, cognitively healthy, family history, AD
Brief summary
Recent data show that marked cell damage precedes the clinical manifestation of Alzheimer's disease (AD). Hence, targeting populations at risk with pharmacological interventions is a possible strategy to lessen the burden of the disease. Cognitively normal individuals with subjective memory complaints (SMC) manifest biological characteristics consistent with early AD and are at risk for future cognitive decline. Family history of AD also constitutes a risk. In a previous study the investigators showed that memantine slows down the accumulation of phosphorylated tau in normal SMC subjects. Using a multivoxel high field MR spectroscopy (MRS) technique, the investigators also demonstrated that memantine decreased hippocampal glutamate. Both these findings may be consistent with the drug's anti-excitotoxic activity. In this new project the investigators propose to treat a sample of 12 presymptomatic individuals at risk (SMC and family history of AD) with memantine. This will be a double blind, placebo controlled study with a control group (12 non-treated subjects). The investigators will determine whether the effects of memantine as assessed by cognitive performance and MRS are present after 4 months of treatment and persist 2 months after discontinuation. MRS will be used to evaluate the effect of memantine on levels of the neurotransmitter glutamate and neuronal viability marker N-acetylaspartate (NAA) in the hippocampus. The investigators will test the following hypotheses: 1. In subjects with SMC, memantine has modifying effects on brain biochemistry as reflected in MRS reductions in glutamate (reduced excitotoxicity) and increases in NAA (neuronal integrity). 2. The effects of the drug persist (as a marker of sustained neuroprotection) and can be measured 2 months after discontinuation of the treatment.
Interventions
DRUGmemantine
participants will be asked to take memantine (20mg/day) for 16 weeks
DRUGPlacebo
participants will be asked to take 2 tablets per day to match active drug
Sponsors
Forest Laboratories
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* presence of subjective memory complaints without objective evidence of impaired cognition * family history of Alzheimer's disease
Exclusion criteria
* major depression * Parkinson's disease * stroke * seizures * uncontrolled diabetes or hypertension * current benzodiazepine use * substance abuse * contraindication for MRI * contraindications for memantine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| N-acetylaspartate | baseline (pre-treatment) and 4 months (post-treatment) | The change in N-acetylaspartate (NAA) measured with magnetic resonance spectroscopy (MRS) is the primary outcome measure. NAA is a metabolite found predominately in neuronal cells, and its amount indicates tissue well being (the higher the better). In MRS studies NAA (and other metabolites like choline or myoinositol) are presented as a ratio to creatine (Cr) also measured by MRS. The concentration of creatine does not change is used as an internal standard. The ratio NAA/Cr is unitless. In summary, the measurable outcome will be the NAA/Cr ratio change from pre-to post treatment. |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study was carried out at the NYU Center for Brain Health and Aging and Dementia Center, between May 2010 and October 2011.
Participants by arm
| Arm | Count |
|---|---|
| Memantine memantine : participants will be asked to take memantine (20mg/day) for 16 weeks | 7 |
| Placebo | 10 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Memantine | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 6 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 1 Participants | 4 Participants |
| Age, Continuous | 69.7 years STANDARD_DEVIATION 7.1 | 69.7 years STANDARD_DEVIATION 5.7 | 69.7 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 17 participants | 7 participants | 10 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 7 | 0 / 10 |
| serious Total, serious adverse events | 1 / 7 | 1 / 10 |
Outcome results
Primary
N-acetylaspartate
The change in N-acetylaspartate (NAA) measured with magnetic resonance spectroscopy (MRS) is the primary outcome measure. NAA is a metabolite found predominately in neuronal cells, and its amount indicates tissue well being (the higher the better). In MRS studies NAA (and other metabolites like choline or myoinositol) are presented as a ratio to creatine (Cr) also measured by MRS. The concentration of creatine does not change is used as an internal standard. The ratio NAA/Cr is unitless. In summary, the measurable outcome will be the NAA/Cr ratio change from pre-to post treatment.
Time frame: baseline (pre-treatment) and 4 months (post-treatment)
Population: This is an intention to treat analysis, based on initial treatment assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Memantine | N-acetylaspartate | pre-treatment | 1.35 NAA/creatine Ratio | Standard Deviation 0.38 |
| Memantine | N-acetylaspartate | post-treatment | 1.58 NAA/creatine Ratio | Standard Deviation 0.005 |
| Placebo | N-acetylaspartate | pre-treatment | 1.86 NAA/creatine Ratio | Standard Deviation 0.43 |
| Placebo | N-acetylaspartate | post-treatment | 1.26 NAA/creatine Ratio | Standard Deviation 0.49 |